Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model

Kyle A. Perry, C. Kristian Enestvedt, Luke W. Hosack, Thai H. Pham, Brian S. Diggs, Swee Teh, Susan Orloff, Shelly Winn, John G. Hunter, Brett C. Sheppard

Research output: Contribution to journalArticle

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Abstract

Background Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells. Methods Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest. Results None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm3 in the open group compared with 180 mm3 in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 ± 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 ± 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 ± 19.6 pg/ml; LR, 26.9 ± 34.5 pg/ml; p = 0.549). Conclusions Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.

Original languageEnglish (US)
Pages (from-to)1151-1157
Number of pages7
JournalSurgical Endoscopy and Other Interventional Techniques
Volume24
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Hepatectomy
Vascular Endothelial Growth Factor A
Hepatocellular Carcinoma
Animal Models
Neoplasms
Liver
Residual Neoplasm
Messenger RNA
Experimental Liver Neoplasms
Residual Volume
Tumor Microenvironment
Buffaloes
Tumor Burden
Reverse Transcriptase Polymerase Chain Reaction
Serum
Immunoenzyme Techniques
Abdomen
Up-Regulation
Thorax
RNA

Keywords

  • Hepatocellular carcinoma
  • Laparoscopic hepatectomy
  • Vascular endothelial growth factor
  • VEGF

ASJC Scopus subject areas

  • Surgery

Cite this

Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model. / Perry, Kyle A.; Enestvedt, C. Kristian; Hosack, Luke W.; Pham, Thai H.; Diggs, Brian S.; Teh, Swee; Orloff, Susan; Winn, Shelly; Hunter, John G.; Sheppard, Brett C.

In: Surgical Endoscopy and Other Interventional Techniques, Vol. 24, No. 5, 05.2010, p. 1151-1157.

Research output: Contribution to journalArticle

Perry, Kyle A. ; Enestvedt, C. Kristian ; Hosack, Luke W. ; Pham, Thai H. ; Diggs, Brian S. ; Teh, Swee ; Orloff, Susan ; Winn, Shelly ; Hunter, John G. ; Sheppard, Brett C. / Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model. In: Surgical Endoscopy and Other Interventional Techniques. 2010 ; Vol. 24, No. 5. pp. 1151-1157.
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abstract = "Background Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells. Methods Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest. Results None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm3 in the open group compared with 180 mm3 in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 ± 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 ± 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 ± 19.6 pg/ml; LR, 26.9 ± 34.5 pg/ml; p = 0.549). Conclusions Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.",
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T1 - Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model

AU - Perry, Kyle A.

AU - Enestvedt, C. Kristian

AU - Hosack, Luke W.

AU - Pham, Thai H.

AU - Diggs, Brian S.

AU - Teh, Swee

AU - Orloff, Susan

AU - Winn, Shelly

AU - Hunter, John G.

AU - Sheppard, Brett C.

PY - 2010/5

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N2 - Background Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells. Methods Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest. Results None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm3 in the open group compared with 180 mm3 in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 ± 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 ± 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 ± 19.6 pg/ml; LR, 26.9 ± 34.5 pg/ml; p = 0.549). Conclusions Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.

AB - Background Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells. Methods Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest. Results None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm3 in the open group compared with 180 mm3 in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 ± 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 ± 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 ± 19.6 pg/ml; LR, 26.9 ± 34.5 pg/ml; p = 0.549). Conclusions Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.

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